Biomimetic Design and Construction of an Artificial Lung

该项目的最终目标是开发用于治疗急慢性疾病的人工肺辅助装置技术。 肺功能衰竭。慢性肺病是美国第三大死因，超过 仅限于心脏病和癌症。目前还没有针对慢性病的长期解决方案，例如 除肺移植外的慢性阻塞性肺疾病(COPD)，严重缺乏 捐献器官限制了这种方法，使大多数患者依赖于家庭氧疗。治疗急性疾病 例如成人呼吸窘迫综合征(ARDS)，通常需要机械通风，以及 并发症和死亡率仍然很高。替代方案，如体外膜氧合器 (ECMO)治疗只能使用有限的时间，需要高水平的抗凝，并涉及 操作上有许多复杂性。迫切需要人工肺的技术进步 设备，包括简化和延长设备的使用，减少对抗凝的需要，以及 气体转移率以紧凑的形式与低血容量。在这里，我们提出了一种探索性的 生物工程研究助学金，致力于生物人工肺技术的开发，基于 构建可伸缩呼吸辅助结构的仿生设计原理和微制造技术 能够在小巧紧凑的结构中进行高水平的气体输送。成功地开发了一个 生物人工肺将需要几个关键要素，其中许多要素尚未实现，因为 由于制造技术的限制，在模拟自然肺生理方面存在困难。具体目标 这一提议针对的是这些元素，包括用 引爆量小，气体渗透性高，并建立内皮化的 微血管网络，在没有抗凝剂的情况下，支持平稳的血液流动，而不会发生凝血。 这些目标与未来的临床目标是一致的，包括为患者提供长期 功能性呼吸辅助设备，不需要广泛的抗凝，可以在 可穿戴或可能可植入的格式。为了实现这些目标，我们的目标是1)产生一种仿生的 设计并利用微加工技术构建包含微血管的人工肺模块 2)建立血管内皮化微流控网络 并测定生物人工肺结构的气体传输和血流凝固特性。

The ultimate goal of this project is to develop artificial lung assist device technology to treat acute and chronic pulmonary failure. Chronic lung disease is the third-leading cause of death in the United States, exceeded only by heart disease and cancer. Currently there are no long-term solutions for chronic diseases such as Chronic Obstructive Pulmonary Disease (COPD) other than lung transplantation, and a severe shortage of donor organs limits this approach, leaving most patients relying on home oxygen therapy. For acute illnesses such as Adult Respiratory Distress Syndrome (ARDS), mechanical ventilation is typically required, and complications and mortality remain very high. Alternatives such as ExtraCorporeal Membrane Oxygenator (ECMO) therapy can only be used for a limited duration, require high levels of anticoagulation and involve numerous operational complexities. There is an urgent need for technological advances in artificial lung devices, including simplification and extended use of devices, a reduced need for anticoagulation, and high gas transfer rates in a compact format with low blood volumes. Here we propose an Exploratory Bioengineering Research Grant to pursue the development of technology for a bioartificial lung, based on biomimetic design principles and microfabrication technology to build scalable respiratory assist architectures capable of high levels of gas transport in a small and compact structure. Successful development of a bioartificial lung will require several critical elements, many of which have not been realized because of difficulties in mimicking natural lung physiology due to limitations in fabrication technology. The specific aims of this proposal are directed towards these elements, including the ability to design a biomimetic structure with small priming volume and high levels of gas permeability, and the establishment of an endothelialized microvascular network to support smooth blood flow without clotting in the absence of anticoagulative agents. These goals are consistent with future clinical targets including the ability to provide patients with long-term functional respiratory assist devices that do not require extensive anticoagulation and that can be enabled in a wearable or potentially implantable format. To accomplish these goals, we aim 1) To generate a biomimetic design and utilize microfabrication technology to construct an artificial lung module comprising microvascular networks and gas-permeable membranes, and 2) To establish endothelialized microfluidic network in vascular chamber and determine gas transport and blood flow coagulation properties of bioartificial lung construct.